Studies indicating that the monocyte may be of major importance in the modulation of B cell activation will be pursued investigating the nature of the mechanisms involved in the regulation of immunoglobulin synthesis. Attempts will be made to develop conditions for the coculture of rheumatoid synovial membrane fragments and rheumatoid cartilage. Methods for the quantitation of Ig synthesis, tritiated thymidine incorporation into DNA in synovial fragments and MIF production by synovial tissue fragments will be validated. Lymph node, peripheral blood and bone marrow lymphocytes will be examined to measure their ability to respond to polyclonal B cell activators; lymphocytes from spleens of aging NZW mice will be continued. Breeding studies will be conducted to determine if the surface immunoglobulin isotype is localized to the X chromosome, or whether it is an autosomal trait. To delineate the cellular site of action of these agents, the effect of gold compounds, penicillamine and mixtures of penicillamine and copper salts on PWM-induced generation of immunoglobulin secreting cells from human peripheral blood cells will be examined; additionally, their effects on the ultrastructural characteristics of cultured human lymphocytes and monocytes will be examined. The evaluation of the effect of gold or D-penicillamine therapy on peripheral blood monocytes and lymphocytes will be studied in patients with rheumatoid arthritis. The mechanism involved in the variation in frequency of Ig deposits from site to site in the normal skin of SLE patients will be examined. Efforts will be continued to identify DNA antibody in material obtained from the skin of SLE patients. The cell surface characteristics of the infiltrating cells of LE skin lesions will be studied using fluorescence-conjugated antisera to stain the tissue. The subepidermal deposits in NZB/W mice will be localized by the immunoperoxidase technique. Studies will be conducted to determine if immune complexes present in sera of Felty's patients cause aggregation of neutrophils and whether these complexes cause adherence of neutrophils to macrophages or endothelial cells. Further, attempts will be made to determine whether endothelial cells obtained from umbilical cord have Fc or C3 receptors and whether these immune complexes cause release of superoxide.